Current Status of Stem Cell Therapy for Sepsis and Acute Respiratory Distress Syndrome

Abstract

Sepsis and acute respiratory distress syndrome (ARDS) are life-threatening diseases with high mortality, around 40%, and morbidity in all the critical care units around the world. After decades of research, and numerous pre-clinical and clinical trials, sepsis and ARDS remain without a specific and effective pharmacotherapy and essentially the management remains supportive. Over the last years, cell therapies gained potential as a therapeutic treatment for ARDS and sepsis. Based on numerous pre-clinical studies, there is a growing evidence of the potential benefits of cell-based therapies for the treatment of sepsis and ARDS. Different cell subtypes have been used for the treatment of both syndromes; however, the major part of the studies is using mesenchymal stem/stromal cells (MSC). Also, other relevant groups performed some pre-clinical studies using induced pluripotent stem cells (iPSC) for the treatment of both syndromes and alveolar type II cells for ARDS treatment. Numerous questions need further study, including determining the best source for the progenitor cells isolation, their large-scale production, and cryopreservation. Also, the heterogeneity of patients with sepsis and ARDS is massive, and the stratification of the patients will help us to determine better the therapeutic effect of these cell therapies. In this review, we are going to describe briefly the different cell types, their potential sources, and characteristics and mechanism of action. We will review several pre-clinical and clinical studies in ARDS and sepsis.

Stem Cell‐based therapies for COVID‐19‐related acute respiratory distress syndrome

“…Mesenchymal stem cells (MSCs) have been given particular attention in recent years as they do not require de‐differentiation as is the case with pluripotent sources, yet can still be induced to lineage‐specific, directed differentiation 40,41 . MSCs can bypass the technical constraints presented by isolating cells from specific organs, or ethical concerns surrounding use of embryonic cells because, they can be harvested from both autologous and allogeneic sources of relatively accessible tissue sources including umbilical cord, bone marrow, adipose tissue, and placenta 42–44 . Careful characterization of these cells, including matching major histocompatibility complex (MHC) and genetic stability testing, may allow the development of a clinical‐grade, ready‐for‐use, allogeneic cell bank sourced from healthy donor stem cells to facilitate prompt administration of MSCs for acute diseases, circumventing time‐sensitive restrictions and technical constraints on the extraction and processing of patient‐derived tissues in point‐of‐care settings that would be required for autologous administration 45 …”